title: The BpeEF-OprC efflux pump is responsible for widespread trimethoprim resistance in clinical and environmental Burkholderia pseudomallei isolates.
abstract: Trimethoprim-sulfamethoxazole (co-trimoxazole) is the primary drug used for oral eradication therapy of Burkholderia pseudomallei infections (melioidosis). Here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast Thailand and northern Australia. This resistance was shown to be due to BpeEF-OprC efflux pump expression. No dihydrofolate reductase target mutations were involved, although frequent insertion of ISBma2 was noted within the putative folA transcriptional terminator. All isolates tested remained susceptible to trimethoprim-sulfamethoxazole, suggesting that resistance to trimethoprim alone in these strains probably does not affect the efficacy of co-trimoxazole therapy.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Podnecky
authors.forename: Vanaporn
authors.initials: V
authors.lastname: Wuthiekanun
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Herbert P
authors.initials: HP
authors.lastname: Schweizer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001315:Australia / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D008554:Melioidosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013728:Terminator Regions, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013785:Thailand / Q000453:epidemiology; D014295:Trimethoprim / Q000494:pharmacology*; D014296:Trimethoprim Resistance / Q000187:drug effects / Q000235:genetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase